Auraptene inhibits migration, invasion and metastatic behavior of human malignant glioblastoma cells: An in vitro and in silico study

• Main Authors: Seyed Hadi Mousavi (Author), Mohammad Jalili-Nik (Author), Mohammad Soukhtanloo (Author), Arash Soltani (Author), Farzaneh Abbasinezhad-Moud (Author), Hamid Mollazadeh (Author), Farzaneh Shakeri (Author), Bahram Bibak (Author), Amirhossein Sahebkar (Author), Amir R. Afshari (Author)
• Format: Book
• Published: Mashhad University of Medical Sciences, 2024-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2228-7930; 2228-7949; 10.22038/ajp.2023.23586
• Keywords: auraptene; glioblastoma multiforme; migration; invasion; metastasis; Therapeutics. Pharmacology; RM1-950
• Source: Avicenna Journal of Phytomedicine, Vol 14, Iss 3, Pp 349-364 (2024)

Objective: The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells.Materials and Methods: To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot analysis were conducted.Results: At sublethal concentrations of 12.5 and 25 µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that the total protein level of MMP-2 as well as phosphorylation of crucial metastasis-related proteins, including p-JNK and p-mTOR, decreased in auraptene-treated cells. The molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3.Conclusion: Auraptene effectively inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities. Auraptene might serve as a potential anti-metastatic agent against malignant GBM.